| http://purl.uniprot.org/citations/33096251 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/33096251 | http://www.w3.org/2000/01/rdf-schema#comment | "Oxidative stress has been associated with pathogenesis in several diseases including Huntington's disease (HD), a neurodegenerative disorder caused by a mutation in the huntingtin gene. Oxidative stress induced reactive oxygen species (ROS) are normally controlled at the cellular level by the nuclear factor (erythroid-derived 2)-like 2 (NRF2) a transcription factor that regulates the expression of various antioxidants and detoxifying proteins. Normally NRF2 is largely inactivated in the cytoplasm by the Kelch-like ECH-associated protein 1 (KEAP1)/Cullin-3 (CUL3) mediated ubiquitination and subsequent proteosomal degradation. In the presence of ROS, KEAP1 sensor cysteines are directly or indirectly engaged resulting in NRF2 release, nuclear translocation, and activation of its target genes. Consequently the activation of NRF2 by a small-molecule drug may have the therapeutic potential to control oxidative stress by upregulation of the endogenous antioxidant responses. Here we attempted to validate the use of a reversible non-acidic KEAP1 binder (Compound 2) to activate NRF2 with better cellular activity than similar acidic compounds. When tested head to head with sulforaphane, a covalent KEAP1 binder, Compound 2 had a similar ability to induce the expression of genes known to be modulated by NRF2 in neurons and astrocytes isolated from wild-type rat, wild type mouse and zQ175 (an HD mouse model) embryos. However, while sulforaphane also negatively affected genes involved in neurotoxicity in these cells, Compound 2 showed a clean profile suggesting its mode of action has lower off-target activity. We show that Compound 2 was able to protect cells from an oxidative insult by preserving the ATP content and the mitochondrial potential of primary astrocytes, consistent with the hypothesis that neurotoxicity induced by oxidative stress can be limited by upregulation of innate antioxidant response."xsd:string |
| http://purl.uniprot.org/citations/33096251 | http://purl.org/dc/terms/identifier | "doi:10.1016/j.freeradbiomed.2020.10.022"xsd:string |
| http://purl.uniprot.org/citations/33096251 | http://purl.uniprot.org/core/author | "Park L."xsd:string |
| http://purl.uniprot.org/citations/33096251 | http://purl.uniprot.org/core/author | "Harper S."xsd:string |
| http://purl.uniprot.org/citations/33096251 | http://purl.uniprot.org/core/author | "Cerretani M."xsd:string |
| http://purl.uniprot.org/citations/33096251 | http://purl.uniprot.org/core/author | "Tomei L."xsd:string |
| http://purl.uniprot.org/citations/33096251 | http://purl.uniprot.org/core/author | "Pacifici R."xsd:string |
| http://purl.uniprot.org/citations/33096251 | http://purl.uniprot.org/core/author | "Bresciani A."xsd:string |
| http://purl.uniprot.org/citations/33096251 | http://purl.uniprot.org/core/author | "Missineo A."xsd:string |
| http://purl.uniprot.org/citations/33096251 | http://purl.uniprot.org/core/author | "Moretti D."xsd:string |
| http://purl.uniprot.org/citations/33096251 | http://purl.uniprot.org/core/author | "Fezzardi P."xsd:string |
| http://purl.uniprot.org/citations/33096251 | http://purl.uniprot.org/core/author | "Sherman L.T."xsd:string |
| http://purl.uniprot.org/citations/33096251 | http://purl.uniprot.org/core/author | "Tambone S."xsd:string |
| http://purl.uniprot.org/citations/33096251 | http://purl.uniprot.org/core/author | "Dominquez C."xsd:string |
| http://purl.uniprot.org/citations/33096251 | http://purl.uniprot.org/core/author | "Munoz-Sajuan I."xsd:string |
| http://purl.uniprot.org/citations/33096251 | http://purl.uniprot.org/core/date | "2021"xsd:gYear |
| http://purl.uniprot.org/citations/33096251 | http://purl.uniprot.org/core/name | "Free Radic Biol Med"xsd:string |
| http://purl.uniprot.org/citations/33096251 | http://purl.uniprot.org/core/pages | "243-254"xsd:string |
| http://purl.uniprot.org/citations/33096251 | http://purl.uniprot.org/core/title | "NRF2 activation by reversible KEAP1 binding induces the antioxidant response in primary neurons and astrocytes of a Huntington's disease mouse model."xsd:string |
| http://purl.uniprot.org/citations/33096251 | http://purl.uniprot.org/core/volume | "162"xsd:string |
| http://purl.uniprot.org/citations/33096251 | http://www.w3.org/2004/02/skos/core#exactMatch | http://purl.uniprot.org/pubmed/33096251 |
| http://purl.uniprot.org/citations/33096251 | http://xmlns.com/foaf/0.1/primaryTopicOf | https://pubmed.ncbi.nlm.nih.gov/33096251 |
| http://purl.uniprot.org/uniprot/#_O89076-mappedCitation-33096251 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/33096251 |
| http://purl.uniprot.org/uniprot/#_Q05DM3-mappedCitation-33096251 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/33096251 |